Amy Lee Joins Biology Faculty

On August 1, Amy Lee joined the Biology department as an Assistant Professor. Previously, Amy was an American Cancer Society Postdoctoral Scholar in Jamie Cate’s lab at University of California, Berkeley. She received her Ph.D. in Virology from Harvard University in Sean Whelan’s lab and her Bachelors of Science in Biology from Massachusetts Institute of Technology.


eIF3d structure, see Figure 2 at

Amy’s research focuses on understanding how gene regulation shapes cell growth and differentiation, and how dysregulation leads to human diseases like carcinogenesis and neurodegeneration. She is interested in discovering new mechanisms of mRNA translation initiation and novel functions of RNA-binding proteins and eukaryotic translation factors. Her research combines genome-wide and computational approaches together with molecular genetics, cell biology, biochemistry, and structural biology techniques.

Amy recently published a paper in Nature together with the Jamie Cate, Jennifer Doudna, and Philip Kranzusch describing the discovery of a new translation pathway that controls the production of proteins critical to regulating the growth and proliferation of cells. Cancer is characterized by uncontrolled cell growth, which means the protein production machinery goes into overdrive to provide the building materials and control systems for new cells. Hence, biologists for decades have studied the proteins that control how genes are transcribed into mRNA and how the mRNA is read and translated into a functioning protein. One key insight more than 40 years ago was that a so-called initiation protein must bind to a chemical handle on the end of each mRNA to start it through the protein manufacturing plant, the ribosome. Until now, this initiation protein was thought to be eIF4E (eukaryotic initiation factor 4E) for all mRNAs.

Amy and her colleagues discovered that for a certain specialized subset of mRNAs – most of which have been linked somehow to cancer – initiation is triggered by a different protein, called eIF3d. The finding was a surprise because the protein is part of an assembly of 13 proteins called eIF3 -eukaryotic initiation factor 3 – that has been known and studied for nearly 50 years, and no one suspected its undercover role in the cell. This may be because eIF3’s ability to selectively control mRNA translation is turned on only when it binds to the set of specialized mRNAs. Binding between eIF3 and these mRNAs opens up a pocket in eIF3d that then latches onto the end-cap of mRNA to trigger the translation process. Subsequent X-ray crystallography of eIF3d revealed the structural rearrangements that must occur when eIF3 binds to the mRNA tag and which open up the cap-binding pocket. eIF3d thus presents a promising new drug target in cancer, as a drug blocking this binding protein could shut off translation of only the growth-promoting proteins and not other life-critical proteins inside the cell.

Lee AS, Kranzusch PJ, Doudna JA, Cate JH. eIF3d is an mRNA cap-binding protein that is required for specialized translation initiation. Nature. 2016.


2012 Rosenstiel Award Recipient, Dr. Nahum Sonenberg

2012 Rosenstiel Award Lecture
Thursday, March 29, 2012, 4:00 PM
Gerstanzang 123

The 2012 Rosenstiel award winner, Dr. Nahum Sonenberg of McGill University, is a well-deserving recipient of this honor. Dr. Sonenberg received his Ph.D. in 1976 at the Weizman Institute of Science.  He then worked with Aaron Shatkin, where he discovered the translation initiation factor responsible for binding the 5’ cap of mRNA, eukaryotic Initiation Factor 4E (eIF4E); He has studied translation ever since.  Although his lab focuses on understanding how the cell achieves precise control of translation initiation, this line of investigation has led to discoveries affecting a wide variety of systems.  His lab has made key discoveries in cancer, obesity, virology, memory consolidation and how translation control plays a role in regulating these disparate processes.

In 1988, the Sonenberg lab made the groundbreaking discovery (Nature 1988, that the uncapped viral mRNA from poliovirus recruits the ribosome to internal regions of the 5’ untranslated region (UTR).  These sites have since been renamed internal ribosomal entry sites (IRESs). This finding was exciting since eukaryotic translation initiation typically requires the 5’ cap on an mRNA for eIF4E binding which subsequently recruits translation initiation machinery.  Until this time, the only mechanism of translation initiation was through the binding of eIF4E to the 5’ cap of mRNAs.  Sonenberg’s discovery that some mRNA has a mechanism to bypass the need for eIF4E binding and thereby avoiding translation control mechanisms started a new line of investigation in the translation field.  Along with discovering IRESs, this paper established an in vitro and an in vivo assay to study cap-independent translation initiation.  These assays are still used widely to test for IRES activity of mRNA UTRs.

Since that initial discovery, it has been found that many viruses contain IRES sequences in the UTR of mRNA that direct translation of viral proteins.  Some viruses, including poliovirus, are able to hijack eukaryotic translation machinery by cleaving factors necessary for canonical cap-dependent translation initiation, but dispensable for IRES translation. In this way, viral mRNAs are able to outcompete eukaryotic mRNAs for ribosome binding and in many cases become the most abundant transcript being translated.

Since the discovery of viral IRESs, many labs, including the Sonenberg lab, have discovered that some cellular genes also use IRESs to bypass the typical translation initiation control mechanisms. These genes are capable of translating even when the cell is actively shutting down translation.  One such cellular IRES-containing mRNA is the insulin receptor message, the IRES I study in the Marr lab.  Using assays similar to those first used in the 1988 paper published by the Sonenberg lab, I am exploring the necessity for the various initiation factors and IRES sequences required for efficient translation of insulin receptor in Drosophila melanogaster and mammalian cells.

The discovery that Dr. Sonenberg made in 1988 is only one example of the elegant research his lab has produced and continues to pursue.

Protected by Akismet
Blog with WordPress

Welcome Guest | Login (Brandeis Members Only)